Labeling of active neural circuits in vivo with designed calcium integrators

被引:325
作者
Fosque, Benjamin F. [1 ]
Sun, Yi [1 ]
Dana, Hod [1 ]
Yang, Chao-Tsung [1 ]
Ohyama, Tomoko [1 ]
Tadross, Michael R. [1 ]
Patel, Ronak [1 ]
Zlatic, Marta [1 ]
Kim, Douglas S. [1 ]
Ahrens, Misha B. [1 ]
Jayaraman, Vivek [1 ]
Looger, Loren L. [1 ]
Schreiter, Eric R. [1 ]
机构
[1] Howard Hughes Med Inst, Ashburn, VA 20147 USA
关键词
NEURONAL-ACTIVITY; GENE-EXPRESSION; VISUAL-CORTEX; DROSOPHILA; BRAIN; PROTEIN; POPULATIONS; SENSOR; CELLS;
D O I
10.1126/science.1260922
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The identification of active neurons and circuits in vivo is a fundamental challenge in understanding the neural basis of behavior. Genetically encoded calcium (Ca2+) indicators (GECIs) enable quantitative monitoring of cellular-resolution activity during behavior. However, such indicators require online monitoring within a limited field of view. Alternatively, post hoc staining of immediate early genes (IEGs) indicates highly active cells within the entire brain, albeit with poor temporal resolution. We designed a fluorescent sensor, CaMPARI, that combines the genetic targetability and quantitative link to neural activity of GECIs with the permanent, large-scale labeling of IEGs, allowing a temporally precise "activity snapshot" of a large tissue volume. CaMPARI undergoes efficient and irreversible green-to-red conversion only when elevated intracellular Ca2+ and experimenter-controlled illumination coincide. We demonstrate the utility of CaMPARI in freely moving larvae of zebrafish and flies, and in head-fixed mice and adult flies.
引用
收藏
页码:755 / 760
页数:6
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